Hereditary and acquired deficiencies of protein C, protein S, and antithrombin III are important risk factors of thrombosis, especially in peripheral veins. In a prospective study, concentrations of these factors were measured to determine the prevalence of deficiencies of these proteins in ocular vascular occlusive disease. A total of 167 patients with acute retinal arterial (28%) or venous occlusion (55%) or ischemic optic neuropathy (17%) were included. Exclusion criteria were anticoagulant therapy, renal insufficiency, and hepatic disease. The mean values obtained for all patients were in normal range (protein C, 102 +/- 25%; protein S, 109 +/- 22%; antithrombin III, 23.6 +/- 3.1 IU/ml). Antithrombin III was pathologically reduced in one patient with branch venous occlusion. Proteins C and S were severely altered in two patients with central venous occlusion, in one individual with ischemic optic neuropathy, and in one patient with branch arterial occlusion. Subnormal values were found in 21 patients for antithrombin III (16.1-19.9 IU/ml), in 7 patients for protein C (55-65%). Two of these five patients with pathologic findings showed severe vascular manifestations in the form of current deep-vein thrombosis and multiple retinal occlusions. Their age was 30 and 53 years, respectively, and differed considerably from the mean age of the entire group (65 +/- 12 years). This study suggests that these proteins were important factors for the development of ocular vascular occlusive diseases in single patients. Although the prevalence is low, measurement of these parameters in young patients may be useful in preventing other vascular complications.